Abstract
Multidrug-resistant Pseudomonas aeruginosa poses a serious problem due to hospital- and healthcare-associated infections. A major drug resistance mechanism of P. aeruginosa involves active efflux via resistance nodulation cell division (RND)-type multidrug efflux pumps of which MexXY is increasingly recognized as a primary determinant of aminoglycoside resistance in P. aeruginosa. MexXY overexpression is often observed in drug-resistant P. aeruginosa clinical isolates. MexXY deficiency increased pyoverdine production in all four P. aeruginosa strains we tested. MexXY-overproducing multidrug-resistant P. aeruginosa PA7 exhibited the greatest effect among the strains. Complementation with a MexXY-expressing plasmid restored low-level pyoverdine production in a MexXY-deficient P. aeruginosa mutant from PA7, indicating that MexXY expression decreases pyoverdine production. Because P. aeruginosa produces pyoverdine to acquire iron, MexXY-deficient mutants might be more susceptible to iron deficiency than MexXY-producing strains or might require extra iron. High-risk clones of multidrug-resistant P. aeruginosa reportedly tend to be MexXY overproducers but defective pyoverdine producers. This study suggests that P. aeruginosa reduces production of a virulence factor after acquiring a drug resistance factor.
Highlights
IntroductionPseudomonas aeruginosa is a known opportunistic pathogen and a major threat in hospital and healthcare-associated environments [1]
We found that strain PA7 ∆mexXY-oprA mutant were more yellow-green in color than those of the PA7 parent strain, which are highly multidrug resistant [13]
We quantitatively examined pyoverdine production by four P. aeruginosa strains in comparison with the corresponding mexXY-deficient mutants (Figure 1)
Summary
Pseudomonas aeruginosa is a known opportunistic pathogen and a major threat in hospital and healthcare-associated environments [1]. Infections caused by P. aeruginosa are often difficult to treat; inappropriate chemotherapy readily selects multidrug-resistant. A major factor in the prominence of P. aeruginosa as a pathogen is its intrinsic resistance to various antibacterial agents [2,3]. One of most important chromosomally encoded antimicrobial resistance factors in P. aeruginosa is resistance nodulation cell-division (RND)-type multidrug efflux pumps [2,4]. Among these pumps, the MexXY system is the only significant determinant of efflux-mediated aminoglycoside resistance in P. aeruginosa [5]. MexXY mediates resistance to other clinically relevant drugs such as cefepime, ciprofloxacin, tigecycline, azithromycin, and colistin [5,6]
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